As part of a continuing effort to test the validity of the critical bilayer theory of assembly as it pertains to membrane instability, we have been examining critical assembly temperatures T* for membrane lipids extracted from normal and diseased neurological tissues. According to the theory if T* is below the physiological temperature, the membranes are unstable and the cells will degenerate. We have previously found this pathogenic mechanism to be applicable in metachromatic leokodystrophy, a disease with a known lipid metabolic defect, and have therefore measured T* for brain tissue with Alzheimer's disease (AD) whose etiology is presently in dispute. For cerebral cortex lipid from these three AD brains T* ranged from 19 to 28 degrees, independent of membrane protein composition. In contrast, control cortex lipids and cerebellar lipids from the AD brains yielded a normal value of 37 degrees. Thus, neurodegeneration in AD may be explicable by membrane destabilization due to a lipid defect. Lipid analysis indicates a significant deficit of plasmalogen PE in AD membranes compared to control membranes.